The dopamine transporter (DAT) has been identified as a principal brain receptor site previously correlated with the rewarding and euphoric properties of cocaine. Euphoric responses to rapid administration of cocaine can be much more prominent than those that follow slower rates of administration. In previous years, investigators in this Branch have found that activators of protein kinase C (PKC) modulate dopamine transport in transiently-expressing COS cells. In the last, we followed previous observations that identified DAT as a phosphoprotein, and identified predominant serine phosphoacceptor sites in phosphoamino acid analyses. Studies of site directed mutants in potential phosphoacceptor sites identify no single residue as a sole site. These data increased evidence that PKC activation enhances levels of DAT phosphorylation at multiple serines, and make phosphorylation an increasingly-strong candidate mechanism for rapid adaptations in dopaminergic systems relevant to cocaine- induced euphoria. While substantial staff reductions experienced suring this year have left us unable to advance the project signficantly during this time, we hope to be able to more it forward in subsequest years. - cocaine amphetamine Parkinson's disease ADHD reward gene structure/function chromosome 5p